Various types of tests related to patient diagnosis and therapy can be performed by analysis assays of a sample of a patient's infections, bodily fluids or abscesses. Such patient samples are typically placed in sample vials, extracted from the vials, combined with various reagents in special reaction cuvettes or tubes, incubated, and analyzed to aid in treatment of the patient. In typical clinical chemical analyses, one or two assay reagents are added at separate times to a liquid sample, the sample-reagent combination is mixed and incubated within a reaction cuvette. Analytical measurements using a beam of interrogating radiation interacting with the sample-reagent combination, for example turbidimetric absorption readings or the like, are made to ascertain end-point or reaction rate values from which the amount of an analyte may be determined using well-known calibration techniques.
Automated clinical analyzers are routinely required to remove all or a portion of sample fluid from collection containers and a number of sampling systems have been produced to assist this operation. Generally, these systems receive sample fluid containers, aspirate or remove a predetermined quantity of sample fluid from each container at a first location, and transfer the aspirated sample fluid to a second location for analysis. The sample fluid containers used with these systems are open-top vials or tubes transported in the system on carousels, racks or linear transports and then transferred between such devices with robotic mechanisms.
Using open sample fluid containers in a clinical laboratory presents a number of problems. First, the various devices which move the containers through the sampling system cause spills and contamination. Second, open sample fluid containers expose an operator to any harmful substances disposed in the containers. Finally, because open containers require special care, the cost of operation increases.
To avoid these problems, sample fluids to be tested in automated clinical analysis systems are often collected in evacuated glass tubes closed with caps like rubber stoppers and sealed with a vacuum. The sample fluid displaces part of the vacuum; but some vacuum may remain. Removal of the closure may result in the formation of aerosol particles. Consequently, when an operator removes the closure before placing the container in the automated system, the aerosol spray may expose the operator to any harmful substances contained in the sample fluid. In addition, removal of the closure manually by the operator increases the cost of operation and decreases the efficiency and reliability of an automated system.
A popular solution to these problems is to present a closed container containing the sample fluid to be analyzed to the automated analysis system and to employ an automated sampling system adapted to aspirate a known amount of sample fluid through the closure of a closed tube or vial. To do so, available sampling system include an arrangement of needles, purge mechanisms, gas pressurization and other complex techniques to take sample fluids from sealed sample fluid containers. In addition to requirements placed on these sampling systems to remove at least a predetermined amount of liquid, concerns remain over the quality of the extracted sample fluid, so that it be free of disruptive non-homogenities like clots or bubbles.
U.S. Pat. No. 4,794,085 describes an apparatus and a method which permit the detection of penetration of liquid by an apertured container used for aspirating and dispensing the liquid. The apparatus has control means for advancing the container an increment of the maximum possible distance to the liquid, means to generate a pressure differential within the dispensing container that is sufficient to generate a signal that is indicative of whether the container aperture is closed by the liquid, and devices to detect and signal the pressure produced within the container by such a pressure differential, and to compare the signaled pressure against a reference.
U.S. Pat. No. 4,926,701 describes a pipetting device comprising a probe for dipping into a reservoir, reaction vessel or the like, a metering pump connected to the probe and a shutoff valve disposed between the probe and the pump are provided. In the intake phase of the pump with the valve open, first air and then a predetermined quantity of liquid is taken in. For at least some of the delivery phase of the pump the valve is in the closed state so that a pressure builds up in the pump. At the end of the delivery phase the valve opens whereby due to the high pressure any adhering liquid particles are expelled.
U.S. Pat. No. 4,951,512 provides for providing access to a sealed container which temporarily provides an opening in the closures of the containers, and either removes contents, senses properties of the contents, or dispenses material into the container. A lift assembly moves each sample fluid container upward against a puncture tube to produce an opening in the closure of the container. The system takes a sample fluid through this opening or inserts a probe through the opening to measure the properties of the sample fluid.
U.S. Pat. No. 5,163,582 covers an apparatus and method for dispensing a predetermined volume of liquid from a closed, liquid-containing blood collection tube is described. The apparatus includes a dual conduit providing a passageway for liquid to be dispensed from a closed blood collection tube and a gas conduit providing a passageway for gas to be introduced into the blood collection tube. Included in the apparatus is insertion of the dual conduit into the blood collection tube, turning the tube away from a vertical, upright orientation, connecting and disconnecting the gas passageway from a gas supply, displacing a volume of gas through the gas passageway, and controlling the operation of the apparatus. A method is also disclosed involving insertion of a dual conduit into a closed blood collection tube, connecting a gas supply to a gas conduit of the dual conduit, rotating the tube away from a vertical, upright orientation, introducing a volume of gas corresponding to a signal into the blood collection tube, receiving a predetermined volume of liquid from the blood collection tube, and physically disconnecting the gas supply from the gas passageway.
U.S. Pat. No. 5,413,246 discloses a disposable apparatus to dispense an amount of liquid from a closed container using a closure piercing means to access the interior of a closed blood collection tube, a gas passage means to allow a metered amount of gas to be forced into the blood collection tube, and a liquid passage means to allow fluid to be dispensed from the tube in proportion to the amount of gas forced into the tube. Also disclosed is a machine which uses a disposable apparatus to dispense liquid from a sequence of closed blood collection tubes in an automated manner. Liquid contained within a blood collection tube is dispensed from the tube by a control means according to signals indicative of the amount of liquid within the tube and the amount of liquid that is desired to be dispensed. A manually operated machine that uses the disposable apparatus to dispense a sample of liquid from a closed blood collection tube is also described.
U.S. Pat. No. 5,499,545 is a method for improving measurement accuracy by eliminating the influence of changes in the atmospheric and internal pressures on the quantity of a liquid absorbed or discharged. A pipetting device inducts a specified quantity of liquid into a tip portion or discharges a specified quantity of liquid from the tip portion by controlling the pressure inside a cylinder portion including a cylinder and a piston. A control target value for the quantity of the liquid to be absorbed or discharged from a command portion and information from an atmospheric pressure measurement portion and a pressure sensor for detecting the internal pressure of the cylinder are sent to a correction calculation portion which in turn performs correction calculation based on measured data on the atmospheric and internal pressures and data on the shapes of the cylinder and tip portion to obtain the distance to be traveled by the piston so that the control target value form the command portion is met. A control portion controls a motor which drives the piston in accordance with information on the distance to be traveled by the piston from the correction calculation portion.
U.S. Pat. No. 5,517,867 discloses an apparatus for extracting a liquid from either an open or a closed liquid container. An upper arm carries a depending single extraction needle at a first lateral end in alignment with a closure penetration axis. A foot attached to a lower arm has a conically shaped surface therein and a central axial bore aligned vertically with the penetration axis. The upper and the lower arms move as a unit until the conically shaped surface on the foot abuts the upper end of a container. This abutting action between the conical surface on the lower arm and the container draws the container into and secures the container in an operating position in which the axis of the container is collinear with the penetration axis. Continued displacement of the upper arm by the actuator with respect to the lower arm extends the extraction needle from the bore and causes the needle to penetrate through the closure. A pair of vertically extending plates is attached to the lower arm. The combination of the plates and the lower arm has sufficient weight to generate a holding force that retains the container in the operating position when an acutator displaces the upper arm to withdraw the extraction needle through the closure and from the container.
U.S. Pat. No. 5,525,298 discloses a device for delivering a serum sample from a blood collection tube into one or more sample vessels or reaction vessels, including a pair of arms which are arranged movably in opposite directions, a motor for driving the arms to selectively grasp the blood collection tube, a block to which the arms are provided, a motor for rotating the block over 135 degrees, a needle-like suction nozzle secured to the block, a syringe having a main body coupled with the suction nozzle and a piston arranged movably within the main body, a motor for driving a piston of the syringe, a slide block on which the block is arranged rotatably, a motor for moving the slide block in right and left directions, a base member arranged movably up and down, and a motor for driving the base member up and down. After the blood collection tube is picked out of a rack by the arms, the base member is moved downward to insert the suction nozzle into the container through the cap, and then the block is rotated to turn over the blood collection tube. Then, the serum sample is sucked by operating the syringe, and then the block is rotated into an initial position. After the suction nozzle is pulled out of the cap, a given amount of the sucked serum sample is discharged into one or more sample vessels or reaction vessels.
U.S. Pat. No. 5,413,067 discloses a sampler mechanism for fluidly interconnecting a ball valve with the interior space of a septum closed container for the taking of closed loop samples of fluid materials. The sampler mechanism includes a needle assembly having a hollow needle and a needle seating collar which is positioned adjacent the ball in the ball valve, a threaded injector end fitting for attaching and securing the needle assembly to the ball valve, and an injector body for fluidly connecting the ball valve to the container and for providing a fluid passageway for fluid communication between the container and a side surface of the injector body.
A common problem in liquid aspirating systems like those described above is the risk of liquid “adhesion” and/or “carryover”. Carryover occurs when a probe having residual traces of a previously dispensed sample or reagent is introduced into volume of a different reagent or sample. Carryover is usually manifested as the contamination of a given reagent supply or a given-sample volume by the introduction thereinto of other reagents or samples that remain on or in or are adsorbed by the sample probe. Adhesion occurs when a portion of an aspirated reagent or sample adheres to the exterior surface of a sample probe and is not appropriately removed therefrom.
To minimize adhesion and/or carryover, the sample fluid probe is generally cleaned by washing prior to subsequent operations. Washing is typically accomplished by lowering the sample fluid probe into a cleaning resource that contains an appropriate cleaning liquid solution. The cleaning liquid solution washes the exterior of the sample fluid probe. The interior of the sample fluid probe is cleaned by aspirating and discharging the cleaning solution. Alternatively, the sample fluid probe may be cleaned by discharging a purge liquid through the sample fluid probe into a drain. Washing may use a jet of drying air forced under pressure through the sample fluid probe or at the exterior surface thereof. In this manner the volume of residual carryover on the exterior surface or the interior of the sample fluid probe is minimized. As a practical matter, cleaning of both the sample fluid probe and cleaning resource is required to preserve proper operation.
Analysis instruments having a typical sample fluid probe wash station are described in U.S. Pat. No. 3,964,526 (Sindermann), U.S. Pat. No. 4,318,885 (Suzuki et al.) and U.S. Pat. No. 3,552,212 (Ohlin), and U.S. Pat. No. 4,323,537 (Mody). A common problem with sample fluid probe washing, however, is residual liquid or contaminants may be adsorbed on the sample fluid probe despite washing. This residue may mix with subsequent sample fluids or reagents drawn into the sample fluid probe and can result in the introduction of a contaminated sample fluid or reagent. Furthermore, the presence of additional residual droplets of sample fluid or reagent on the exterior or interior of the sample fluid probe may cause unwanted additional liquid to be introduced into a destination receptacle. This unwanted residue may mix with subsequent sample fluid or reagents drawn into the sample fluid probe and interfere with chemical analyses. Sample fluid probe cleaning is a particularly troublesome problem when exacerbated by the trend to smaller and smaller sample fluid volumes. A minute volume of cleaning liquid solution may remain within or on the exterior surface of a sample fluid probe causing a corresponding deficiency in the volume of sample fluid later transferred to a reaction vessel. Such a sample fluid volume deficiency may create serious analytical errors in automated assays for calcium, magnesium and glucose, in particular.
U.S. Pat. No. 8,827,744 discloses a method for cleaning a liquid sample probe in which the probe is positioned within a washing chamber inside a wash body and a purging liquid solution is pumped through the probe into the chamber. A cleaning liquid solution may also be pumped into the chamber around the probe. Either or both liquids are subsequently vacuumed from the chamber drawing air through an annular gap between the probe and the wash body thereby creating a cleaning air flow between the exterior probe surface and the wash body. The cleaning air flow removes all cleaning liquid solution and/or purging liquid solution as the probe is removed from the wash body.
U.S. Pat. No. 5,297,794 addresses this problem by using flushing water in combination with an inclined waterway channel in which the sample probe is immersed. As the sample probe traverses the waterway channel, it is withdrawn and liquid communication between the waterway and the sample probe is broken and cleaning ceases, leaving liquid droplets on the sample probe.
U.S. Pat. No. 5,408,891 also addresses this problem and used a wash collar with (1) pressurized water supplied through the inner bore of a fluid sample probe to wash the inside of the sample probe, and (2) a separate supply of water washing the sample probe and the exterior of the sample probe when positioned in a small central chamber within the wash collar. The wash collar is of complex design including five differently shaped portions through a central bore in which the sample probe moves. The water is drawn away from the sample probe and out of the wash collar through a vacuum port located in the lower portion of the bore and in communication with a vacuum source. Unfortunately, only a small portion of external air enters the wash collar from the direction of sample probe insertion, the majority coming from an enlarged lowermost portion of the wash collar bore. This does not permit thorough cleaning of the sample probe.
Accordingly, from a study of the different approaches taken in the prior art to the problems presented by the necessity for aspirating a liquid from a closed liquid container with a sample fluid probe, coupled with the necessity for effectively cleaning the sample fluid probe between sample fluid aspirations within an automated clinical analyzer, it is believed advantageous to provide a cleaning method which effectively eliminates extraneous material from the full interior and the full exterior of a sample fluid probe while at the same time not unduly adding to the complexity of washing resources. It is believed to be highly advantageous for such a sampling system to be adapted to aspirate liquid from a closed liquid container without complex control mechanisms or unduly adding to the aspiration resources required.